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In order to propose a course of action to be taken in the face of any hyperhomocysteinemia, we have reported for the first time in a French journal the recommendations made within the framework of the European E-HOD project for the diagnosis and treatment of remethylation disorders. The remethylation route ensures homocysteine-methionine conversion. It is linked to the folate cycle and the intracellular metabolism of cobalamins. Remethylation disorders can be classified into three groups: 1) isolated disorders (cblD-HC, cblE, cblG) corresponding to an isolated deficit in the production of methylcobalamin, cofactor of methionine synthase; 2) combined disorders (cblC, cblD-MMA/HC, cblF, cblJ) corresponding to an alteration of the transport and intracellular metabolism of cobalamins, which causes a defect in the synthesis of the two functional forms of cobalamin: methylcobalamin and adenosylcobalamin, a cofactor for methyl malonylCoA mutase; 3) MTHFR deficit, an abnormality of the folate cycle. The biological anomalies observed are hyperhomocysteinemia and hypomethioninaemia associated in the case of disorders combined with increased urinary excretion of methylmalonic acid. The clinical presentation is however heterogeneous according to the remethylation disorder but also for the same pathology according to the age. Given the large number of pathologies grouped together in remethylation disorders, this point is illustrated by only two clinical cases concerning the same deficit (deficit in MTHFR) but with different discovery circumstances: a neonatal form and a late form.

International audience; Objective: The study aimed to evaluate the impact of prenatal maternal stress on birth weight using a large cohort of predominantly Caucasian women living in an urban area. Method: Women were recruited between 2005 and 2010. Data collection took place between the 24th and the 28th week of gestation. The Measure of Psychological Stress (MSP-9), a validated tool to assess stress symptoms, was used to collect data on prenatal maternal stress (independent variable). Birth weight (dependent variable) was classified as low birth weight (LBW; 2,500 g), normal birth weight (NBW; 2,500-4,000 g), and macrosomia (>4,000 g). Adjusted odd ratios (aOR) were obtained after performing multivariate logistic regressions adjusted for potential cofounders. At the final stage, 5,721 women were included in analysis. Results: When compared with women experiencing low stress, participants with high-stress scores were at increased risk of delivering an infant with LBW before adjustment [OR = 2.06, 95% CI (1.04-4.09)], but, after adjustment, only a nonsignificant trend remained. However, women experiencing intermediate and high levels of stress were at increased risk of delivering a baby with macrosomia, even after adjustment [aOR = 1.23 ; 95% CI (1.02-1.49)] and [aOR = 1.76 ; 95% CI (1.11-2.77)] compared to those who scored low on the psychological stress scale. Conclusion: Women exposed to high self-reported psychological stress during second trimester (24 th to 28 th weeks) of pregnancy have a 1.7-fold increased risk for delivering a baby with macrosomia when compared to women exposed to low psychological stress.

International audience; Background: Leptin is a satiety hormone mainly produced by white adipose tissue. Decreasing levels have been described following acute stress. Objective: To conduct a systematic review and meta-analysis to determine if leptin can be a biomarker of stress, with levels decreasing following acute stress. Methods: PubMed, Cochrane Library, Embase, and ScienceDirect were searched to obtain all articles studying leptin levels after acute stress on 15 February 2021. We included articles reporting leptin levels before and after acute stress (physical or psychological) and conducted random effects meta-analysis (DerSimonian and Laird approach). We conducted Meta-regressions and sensitivity analyses after exclusion of groups outside the metafunnel. Results: We included seven articles—four cohort and three case-control studies—(28 groups) from 27,983 putative articles. Leptin levels decreased after the stress intervention (effect size = −0.34, 95%CI −0.66 to −0.02) compared with baseline levels, with a greater decrease after 60 min compared to mean decrease (−0.45, −0.89 to −0.01) and in normal weight compared to overweight individuals (−0.79, −1.38 to −0.21). There was no difference in the overweight population. Sensitivity analyses demonstrated similar results. Levels of leptin after stress decreased with sex ratio—i.e., number of men/women—(−0.924, 95%CI −1.58 to −0.27) and increased with the baseline levels of leptin (0.039, 0.01 to 0.07). Conclusions: Leptin is a biomarker of stress, with a decrease following acute stress. Normal-weight individuals and women also have a higher variation of leptin levels after stress, suggesting that leptin may have implications in obesity development in response to stress in a sex-dependent manner.

International audience; The purpose of this study was to determine whether magnesium L-lactate is responsible for having a beneficial effect on the myocardium and the skeletal muscles and how this substrate acts at the molecular level. Twenty seven young male Wistar rats were supplied with a magnesium L-lactate (L) solution, a magnesium chloride (M) solution and/or water (W) as a vehicle for 10 weeks. The treated animals absorbed the L and M solutions as they wished since they also had free access to water. After 9 weeks of treatment, in vivo cardiac function was determined ultrasonically. The animals were sacrificed at the end of the tenth week of treatment and the heart was perfused according to the Langendorff method by using a technique allowing the determination of cardiomyocyte activity (same coronary flow in the two groups). Blood was collected and skeletal muscles of the hind legs were weighed. The myocardial expressions of the sodium/proton exchange 1 (NHE1) and sodium/calcium exchange 1 (NCX1), intracellular calcium accumulation, myocardial magnesium content, as well as systemic and tissue oxidative stress, were determined. Animals of the L group absorbed systematically a low dose of L-lactate (31.5 ± 4.3 µg/100 g of body weight/day) which was approximately four times higher than that ingested in the W group through the diet supplied. Ex vivo cardiomyocyte contractility and the mass of some skeletal muscles (tibialis anterior) were increased by the L treatment. Myocardial calcium was decreased, as was evidenced by an increase in total CaMKII expression, without any change in the ratio between phosphorylated CaMKII and total CaMKII. Cardiac magnesium tended to be elevated. Our results suggest that the increased intracellular magnesium concentration was related to L-lactate-induced cytosolic acidosis and to the activation of the NHE1/NCX1 axis. Interestingly, systemic oxidative stress was reduced by the L treatment whereas the lipid profile of the animals was unaltered. Taken together, these results suggest that a chronic low-dose L-lactate intake has a beneficial health effect on some skeletal muscles and the myocardium through the activation of the NHE1/NCX1 axis, a decrease in cellular calcium and an increase in cellular magnesium. The treatment can be beneficial for the health of young rodents in relation to chronic oxidative stress-related diseases.

Mild traumatic brain injury (mTBI) is one of the common causes of emergency department visits around the world. Up to 90% of injuries are classified as mTBI. Cranial computed tomography (CCT) is a standard diagnostic tool for adults with mTBI. Alternatively, children can be admitted for inpatient observation with CCT scans performed only on those with clinical deterioration. The use of blood biomarkers is a supplementary tool for identifying patients at risk of intracerebral lesions who may need imaging. This review provides a contemporary clinical and laboratory framework for blood biomarker testing in mTBI management. The S100B protein is used routinely in the management of mTBI in Europe together with clinical guidelines. Due to its excellent negative predictive value, S100B protein is an alternative choice to CCT scanning for mTBI management under considered, consensual and pragmatic use. In this review, we propose points to help clinicians and clinical pathologists use serum S100B protein in the clinical routine. A review of the literature on the different biomarkers (GFAP, UCH-L1, NF [H or L], tau, H-FABP, SNTF, NSE, miRNAs, MBP, β trace protein) is also conducted. Some of these other blood biomarkers, used alone (GFAP, UCH-L1) or in combination (GFAP + H-FABP ± S100B ± IL10) can improve the specificity of S100B.

International audience; Background: Mild traumatic brain injury (mTBI) management in emergency departments is a complex process involving clinical evaluation, laboratory testing, and computerized tomography (CT) scanning. Protein S100B has proven to be a useful blood biomarker for early evaluation of mTBI, as it reduces the required CT scans by one-third. However, to date, the ability of S100B to identify positive abnormal findings in the CT scans of patients suffering from mTBI caused by ski practice has not been investigated. Thus, the primary aim of this study was to investigate the diagnostic performance of S100B as an mTBI management biomarker in patients with ski-related mTBI. Materials and Methods: One hundred and thirty adult mTBI patients presenting to the emergency department of Hôpital du Valais in Sion, Switzerland, with a Glasgow Coma Scale (GCS) score of 13-15 and clinical indication for a CT scan were included in the study. Blood samples for S100B measurement were collected from each patient and frozen in 3-hour post-injury intervals. CT scans were performed for all patients. Later, serum S100B levels were compared to CT scan findings in order to evaluate the biomarker's performance. Results: Of the 130 included cases of mTBI, 87 (70%) were related to ski practice. At the internationally established threshold of 0.1 μg/L, the receiver operating characteristic curve of S100B serum levels for prediction of abnormal CT scans showed 97% sensitivity, 11% specificity, and a 92% negative predictive value. Median S100B concentrations did not differ according to sex, age, or GCS score. Additionally, there was no significant difference between skiers and non-skiers. However, a statistically significant difference was found when comparing the median S100B concentrations of patients who suffered fractures or had polytrauma and those who did not suffer fractures. Conclusion: The performance of S100B in post-mTBI brain lesion screenings seems to be affected by peripheral lesions and/or ski practice. The lack of neurospecificity of the biomarker in this context does not allow unnecessary CT scans to be reduced by one-third as expected.

Many inherited metabolic diseases (IMD) have cardiac manifestations. The aim of this study was to estimate the prevalence of IMD in adult patients with hypertrophic cardiomyopathy (HCM) and cardiac rhythm abnormalities that require cardiac implantable electronic devices (CIEDs). The study included a review of the medical files of patients aged 18 to 65 years who were followed in our cardiology department during the period 2010&ndash, 2017. Metabolic explorations for Fabry disease (FD), mitochondrial cytopathies, and fatty-acid metabolism disorders were carried out in patients with unexplained etiology. The prevalence of IMD in patients with HCM was 5.6% (confidence interval (CI): 2.6&ndash, 11.6). Six cases of IMD were identified: 1 mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, 1 Hurler syndrome, 2 Friedreich&rsquo, s ataxia, 1 FD, and 1 short-chain acyl-CoA dehydrogenase deficiency. Three cases of IMD were identified in patients requiring CIEDs: 1 patient with Leber hereditary optic neuropathy, 1 FD, and 1 short chain acyl-CoA dehydrogenase (SCAD) deficiency. IMD prevalence in patients with CIEDs was 3.1% (CI: 1.1&ndash, 8.8). IMD evaluation should be performed in unexplained HCM and cardiac rhythm abnormalities adult patients, since the prevalence of IMD is relatively important and they could benefit from specific treatment and family diagnosis.

International audience; Evaluating the activity of cardiac mitochondria is probably the best way to estimate early cellular damage in chronic pathology. Early diagnosis allows rapid therapeutic intervention thus increasing patient survival rate in a number of diseases. However, data on human cardiac mitochondria are scarce in the international literature. Here, we describe a method to extract and study functional mitochondria from the small-sized right atrial aliquots (minimum of 400 mg) obtained during extracorporeal circulation and usually considered as surgical waste products. The mitochondria were purified through several mechanical processes (fine myocardial cutting, tissue grinding and potter Elvehjem homogenising), an enzymatic proteolytic action (subtilisin) and differential centrifugations. In chronic pathologies, including obesity, early disturbances of mitochondrial function can occur. The effects of obesity on the rate of mitochondrial oxygen consumption and H2O2 release were thus determined with three different substrates (glutamate/malate, succinate/rotenone and palmitoylcarnitine/malate). The human atrial mitochondria were of high quality from a functional viewpoint, compared to rat ventricle organelles, but the extraction yield of the human mitochondria was twice lower than that of rat mitochondria. Tests showed that glutamate/malate-related ADP-stimulated respiration was strongly increased in obese subjects, although the oxidation of the other two substrates was unaffected. Reactive oxygen species (ROS) production by the isolated mitochondria was low in comparison with that of the lean subjects. These results confirm those found in one of our previous studies in the ventricles of rats fed a high-fat diet. In conclusion, the described method is simple, reliable and sensitive. It allows for the description of the impact of obesity on the function of atrial mitochondria while using only a small patient sampling (n = 5 in both the lean and the obese groups).

Background and objective Elevated driving pressure (ΔP) may be associated with increased risk of acute respiratory distress syndrome (ARDS) in patients admitted via the emergency department and with post-operative pulmonary complications in surgical patients. This study investigated the association of higher ΔP with the onset of ARDS in a high-risk, intensive care unit (ICU) population. Methods This is a secondary analysis of a prospective multicentre observational study. Data for this ancillary study were obtained from intubated adult patients with at least one ARDS risk factor upon ICU admission enrolled in a previous multicentre observational study. Patients were followed up for the development of ARDS within 7 days (primary outcome). Univariate and multivariate analyses tested the association between ΔP (measured at ICU admission (baseline) or 24 h later (day 1)) and the development of ARDS. Results A total of 221 patients were included in this study, among whom 34 (15%) developed ARDS within 7 days. These patients had higher baseline ΔP than those who did not (mean ± SD: 12.5 ± 3.1 vs 9.8 ± 3.4 cm H2 O, respectively, P = 0.0001). The association between baseline ΔP and the risk of developing ARDS was robust to adjustment for baseline tidal volume, positive-end expiratory pressure, illness severity, serum lactate and sepsis, pneumonia, severe trauma and shock as primary ARDS risk factors (odds ratio: 1.20; 95% CI: 1.03-1.41; P = 0.02). The same results were found with day 1 ΔP. Conclusion Among at-risk ICU patients, higher ΔP may identify those who are more likely to develop ARDS.

We investigated the association of outcomes with pre-pregnancy body mass index (ppBMI), Institute of Medicine (IOM) recommendations about gestational weight gain, and weight gain trajectories during pregnancy. A prospective cohort of 7866 pregnant women was recruited. ppBMI and weight gain at each follow up visit were collected. The outcomes were gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), caesarean delivery, macrosomia, small (SGA) and large (LGA) for gestational age, neonatal hypoglycemia. Group-based multi-trajectory modelling was used for weight kinetics during pregnancy. In the third trimester, 53.8% of women were above IOM recommendations, with an increased relative risk (RR) of HDP (1.91 (1.40&ndash, 2.61)), caesarean (1.34 (1.15&ndash, 1.56)), macrosomia (2.17 (1.77&ndash, 2.67)), LGA (2.26 (1.83&ndash, 2.80)), and hypoglycemia (1.89 (1.12&ndash, 3.18)). Women with a weight gain above IOM recommendations in the second trimester who normalized their weight gain in third trimester had, compared to those who remained above IOM recommendations, fewer events of HDP (2.8% versus 5.3%, p = 0.008), caesarean delivery (16.9% versus 22%, p = 0.006), macrosomia (8.3% versus 14.2%, p &lt, 0.001), and LGA (7% versus 13.2%, p &lt, 0.001). Multi-trajectory modelling identified three profiles with continued variation in RR of complications, including GDM. Weight gain above IOM recommendations increased the risk of perinatal complications. A correction of excessive weight gain in the second trimester reduces these risks.

We revisited risk factors and outcomes related to the preterm premature rupture of membranes (PPROM). A total of 7866 pregnant women were recruited during 5 years at their first prenatal visit to the perinatal clinic of the institution. We compared three groups (women without prematurity, women with spontaneous preterm labor with intact membranes (sPL with IM), women with PPROM) regarding 60 criteria about characteristics, lifestyle, medical, gynecological, obstetrical history of mothers, medication during pregnancy, events at delivery, and complications in neonates. Logistic regression analyses adjusting for potential confounding factors were used. Of the 6968 women selected, 189 (2.8%) presented a PPROM, and 225 (3.2%) an sPL with IM. The specific risk factors for PPROM were body mass index (BMI) &lt, 18.5 kg/m2 (adjusted odds ratio, aOR: 2.00 (1.09&ndash, 3.67)), history of PPROM (aOR: 2.75 (1.19&ndash, 6.36)), nulliparity (aOR: 2.52 (1.77&ndash, 3.60)), gestational diabetes (aOR: 1.87 (1.16&ndash, 2.99)), and low level of education (aOR: 2.39 (1.20&ndash, 4.78)). The complications associated with PPROM were abruption placentae, cesarean, APGAR 5&prime, &lt, 4, birth weight &lt, 2500 g, stillbirth, neonatal jaundice, and hospitalization of mother and neonates. All these complications were also associated with sPL with IM. Our study confirms some of the risk factors of PPROM and highlights a new one: gestational diabetes. Outcomes of PPROM are related to prematurity.

IntroductionS100B serum analysis in clinical routine could reduce the number of cranial CT (CCT) scans performed on children with mild traumatic brain injury (mTBI). Sampling should take place within 3 hours of trauma and cut-off levels should be based on paediatric reference ranges. The aim of this study is to evaluate the utility of measuring serum S100B in the management of paediatric mTBI by demonstrating a decrease in the number of CCT scans prescribed in an S100B biomonitoring group compared with a ‘conventional management’ control group, with the assumption of a 30% relative decrease of the number of CCT scans between the two groups.Methods and analysisThe protocol is a randomised, multicentre, unblinded, prospective, interventional study (nine centres) using a stepped wedge cluster design, comparing two groups (S100B biomonitoring and control). Children in the control group will have CCT scans or be hospitalised according to the current recommendations of the French Society of Paediatrics (SFP). In the S100B biomonitoring group, blood sampling to determine serum S100B protein levels will take place within 3 hours after mTBI and subsequent management will depend on the assay. If S100B is in the normal range according to age, the children will be discharged from the emergency department after 6 hours’ observation. If the result is abnormal, CCT scans or hospitalisation will be prescribed in accordance with current SFP recommendations. The primary outcome measure will be the proportion of CCT scans performed (absence/presence of CCT scan for each patient) in the 48 hours following mTBI.Ethics and disseminationThe protocol presented (Version 5, 03 November 2017) has been approved by the ethics committee Comité de Protection des Personnes sud-est 6 (first approval 08 June 2016, IRB: 00008526). Participation in the study is voluntary and anonymous. The study findings will be disseminated in international peer-reviewed journals and presented at relevant conferences.Trial registration numberNCT02819778.

International audience; Background - The individual performances and the complementarity of Crohn's disease (CD) activity index (CDAI), C-reactive protein (CRP) and faecal calprotectin (Fcal) to monitor patients with CD remain poorly investigated in the era of "tight control" and "treat to target" strategies. Aim - To assess CDAI, CRP and Fcal variation, alone or combined, after 12 wk (W12) of anti-tumor necrosis factor (TNF) therapy to predict corticosteroids-free remission (CFREM = CDAI < 150, CRP < 2.9 mg/L and Fcal < 250 μg/g with no therapeutic intensification and no surgery) at W52. Methods - CD adult patients needing anti-TNF therapy with CDAI > 150 and either CRP > 2.9 mg/L or Fcal > 250 μg/g were prospectively enrolled. Results - Among the 40 included patients, 13 patients (32.5%) achieved CFREM at W52. In univariable analysis, CDAI < 150 at W12 ( = 0.012), CRP level < 2.9 mg/L at W12 ( = 0.001) and Fcal improvement at W12 (Fcal < 300 μg/g; or, for patients with initial Fcal < 300 μg/g, at least 50% decrease of Fcal or normalization of Fcal (< 100 μg/g) ( = 0.001) were predictive of CFREM at W52. Combined endpoint (CDAI < 150 and CRP ≤ 2.9 mg/L and FCal improvement) at W12 was the best predictor of CFREM at W52 with positive predictive value = 100.0% (100.0-100.0) and negative predictive value = 87.1% (75.3-98.9). In multivariable analysis, Fcal improvement at W12 [odd ratio (OR) = 45.1 (2.96-687.9); = 0.03] was a better predictor of CFREM at W52 than CDAI < 150 [OR = 9.3 (0.36-237.1); = 0.145] and CRP < 2.9 mg/L (0.77-278.0; = 0.073). Conclusion - The combined monitoring of CDAI, CRP and Fcal after anti-TNF induction therapy is able to predict favorable outcome within one year in patients with CD.

International audience; BACKGROUND:We investigated the association between antidepressant and anxiolytic exposure during the first and early second trimester of pregnancy (

Diabetes is characterized by a high mortality rate which is often associated with heart failure. Green tea and eicosapentaenoic acid (EPA) are known to lessen some of the harmful impacts of diabetes and to exert cardio-protection. The aim of the study was to determine the effects of EPA, green tea extract (GTE), and a combination of both on the cardiac consequences of diabetes mellitus, induced in Wistar rats by injection of a low dose of streptozotocin (33 mg/kg) combined with a high fat diet. Cardiac mechanical function, coronary reactivity, and parameters of oxidative stress, inflammation, and energy metabolism were evaluated. In the context of diabetes, GTE alone limited several diabetes-related symptoms such as inflammation. It also slightly improved coronary reactivity and considerably enhanced lipid metabolism. EPA alone caused the rapid death of the animals, but this effect was negated by the addition of GTE in the diet. EPA and GTE combined enhanced coronary reactivity considerably more than GTE alone. In a context of significant oxidative stress such as during diabetes mellitus, EPA enrichment constitutes a risk factor for animal survival. It is essential to associate it with the antioxidants contained in GTE in order to decrease mortality rate and preserve cardiac function.

BackgroundThe receptor for advanced glycation end products (RAGE) modulates the pathogenesis of acute respiratory distress syndrome (ARDS). RAGE inhibition was recently associated with attenuated lung injury and restored alveolar fluid clearance (AFC) in a mouse model of ARDS. However, clinical translation will first require assessment of this strategy in larger animals.MethodsForty-eight anaesthetised Landrace piglets were randomised into a control group and three treatment groups. Animals allocated to treatment groups underwent orotracheal instillation of hydrochloric acid i) alone; ii) in combination with intravenous administration of a RAGE antagonist peptide (RAP), a S100P-derived peptide that prevents activation of RAGE by its ligands, or iii) in combination with intravenous administration of recombinant soluble (s)RAGE that acted as a decoy receptor. The primary outcome measure was net AFC at 4 h. Arterial oxygenation was assessed hourly for 4 h and alveolar-capillary permeability, alveolar inflammation, lung histology and lung mRNA expression of the epithelial sodium channel (α1-ENaC), α1-Na,K-ATPase and aquaporin (AQP)-5 were assessed at 4 h.FindingsTreatment with either RAP or sRAGE improved net AFC rates (median [interquartile range], 21.2 [18.8–21.7] and 19.5 [17.1–21.5] %/h, respectively, versus 12.6 [3.2–18.8] %/h in injured, untreated controls), improved oxygenation and decreased alveolar inflammation and histological evidence of tissue injury after acid-induced ARDS. RAGE inhibition also restored lung mRNA expression of α1-Na,K-ATPase and AQP-5.InterpretationRAGE inhibition restored AFC and attenuated lung injury in a piglet model of acid-induced ARDS.FundingAuvergne Regional Council, Agence Nationale de la Recherche, Direction Générale de l’Offre de Soins.Research in ContextEvidence before this studyThe acute respiratory distress syndrome (ARDS), a clinical syndrome of diffuse pulmonary oedema and inflammation, currently lacks effective therapies and is associated with high mortality and morbidity. The degrees of lung epithelial injury and of alveolar fluid clearance (AFC) impairment, as evaluated by plasma levels of soluble receptor for glycation end-products (RAGE), are major prognostic factors in ARDS and potential therapeutic targets for ongoing research. For example, targeting RAGE with recombinant sRAGE or an anti-RAGE monoclonal antibody has proven beneficial in a translational mouse model of acid-induced ARDS.Added value of this studyIn a piglet model of acid-induced ARDS, treatment with RAGE antagonist peptide or recombinant sRAGE restored AFC and attenuated the features of lung injury, thereby confirming, in the closest evolutionary model species to humans, previous evidence from rodent models that modulation of RAGE may be a therapeutic option for ARDS. Although this is an important step towards future clinical translation, future studies should assess the best methods to modulate RAGE and further confirm the safety of manipulating this pathway in patients with ARDS.

Background: This study’s primary objective was to validate the routine use of S100B via a prospective study. The aim was a reduction of cranial computed tomography (CCT) scans by 30%. The secondary goal was to investigate the influence of age and associated risk factors on the reduction of CCT. Methods: S100B (sampling within 3 h postinjury) was used for patients with mild traumatic brain injury (mTBIs) presenting a medium risk of complications and requiring a CCT scan. Patients with negative S100B (S100B−) were discharged without a CCT scan. Results: Of the 1449 patients included in this study, 468 (32.3%) had S100B− with a sensitivity of 96.4% (95% CI: 87.5%–99.6%), a specificity of 33.4% (95% CI: 31%–36%) and a negative predictive value of 99.6% (95% CI: 98.5%–99.9%). No significant difference in serum levels or the S100B+ rate was observed if patients had retrograde amnesia (0.16 μg/L; 63.8%), loss of consciousness (0.13; 63.6%) or antiplatelet therapy (0.20; 77.9%). Significant differences were found between the S100B concentrations and S100B positivity rates in patients >65 years old and all the groups with patients 65 years old (n=504). Conclusions: The clinical use of S100B in mTBI management reduces the use of CCTs by approximately one-third; furthermore, the percentage of CCTs reduction is influenced by the age of the patient.

CONTEXT: The usefulness of S100B has been noted as a biomarker in the management of mild traumatic brain injury (mTBI) in adults. However, S100B efficacy as a biomarker in children has previously been relatively unclear. OBJECTIVE: A meta-analysis is conducted to assess the prognostic value of S100B in predicting intracerebral lesions in children after mTBI. DATA SOURCES: Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and Google Scholar. STUDY SELECTION: Studies including children suffering mTBI who underwent S100B measurement and computed tomography (CT) scans were included. DATA EXTRACTION: Of 1030 articles screened, 8 studies met the inclusion criteria. RESULTS: The overall pooled sensitivity and specificity were 100% (95% confidence interval [CI]: 98%–100%) and 34% (95% CI: 30%–38%), respectively. A second analysis was based on the collection of 373 individual data points from 4 studies. Sensitivity and specificity results, obtained from reference ranges in children with a sampling time LIMITATIONS: Only patients undergoing both a CT scan and S100B testing were selected for evaluation. CONCLUSIONS: S100B serum analysis as a part of the clinical routine could significantly reduce the number of CT scans performed on children with mTBI. Sampling should take place within 3 hours of trauma. Cutoff levels should be based on pediatric reference ranges.

Background Minor head traumatisms are a common reason for consultation in paediatric emergency departments. The diagnosis of traumatic brain injuries involves performing a cranial computed tomography (CCT), associated with a risk of cancer due to the radiation. The serum S100B is an effective biomarker used to reduce reliance on CCT. While reference ranges have been determined, the limited number of cases regarding infants less than 4 months of age has not allowed this biomarker to be used with this age group. Our study aimed to determine reference ranges for serum S100B based on a larger number of infants from birth to 4 months of age. Methods Three centres included infants coming to the hospital for whom blood samples were taken. These samples were analysed to determine the upper reference values based on the 95th percentile. Results 135 samples were analysed. The upper reference value was 0.51 μg/L for children aged 0 to 4 months. There was no effect of the gender. Conclusions This study provides serum S100B reference ranges based on the largest group of neurologically healthy 0 to 4-month-old infants analysed to date. Reliable reference values of S100B for children are now determined. It is the first step towards validation of thresholds for studies integrating S100B into a clinical decision rule for MHT in children.

International audience; Mitochondrial fatty acid oxidation is a vital biochemical process for energy metabolism. Among the known fatty-acid metabolism disorders, very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency count among the most frequent. Both are potentially very serious diseases as they carry a risk of severe neurological post-crisis sequelae, and even sudden death. Diagnosis relies on plasma acylcarnitine profile analysis and urine organic acid analysis, followed by genetic testing to confirm diagnosis. However, in some cases, it is crucial to run a specific diagnostic assay for enzyme activity, which is generally performed in leukocytes or fibroblasts. The aim of this study was to address this need, first by developing a MCAD and VLCAD enzyme activity-specific diagnostic assay in fibroblasts (by measuring the reaction products, i.e. enoyl-CoA) via a rapid LC-MS/MS-based technique, and then by testing MCAD-deficient patients (n = 6), VLCAD-deficient patients (n = 10), and control patients (n = 12). MCAD activity was significantly different in the MCAD-deficiency (MCADD) group (mean = 0.07 nmol C8:1 formed/min/mg protein) compared to the control group (mean = 0.36 nmol C8:1 formed/min/mg protein). All MCADD patients showed less than 35% residual MCAD activity. VLCAD activity was significantly decreased in the VLCADD group (mean = 0.06 nmol C16:1 formed/min/mg protein) compared to the control group (mean = 0.86 nmol C16:1 formed/min/mg protein, respectively). All VLCADD patients showed less than 35% residual VLCAD activity. This technique allowed also to confirm that a novel ACADVL gene mutation (c.1400T\textgreaterC) is responsible for a defective VLCAD activity (residual activity at 10%).

The incidence of concussion in professional direct-contact sports, particularly in rugby, has increased in recent years. To date, cognitive assessment is the most common means of determining whether a concussed player can return to the game. Serum S100B assay, an objective blood test known to be useful in brain injury management, may offer a novel additional approach to the management of concussed male rugby players. The aim of this study was to investigate the S100B utility for the determination of concussion in a professional 15-players-a-side rugby team. Thirty-nine male rugby players were included in a prospective study during the 2014–2015 French championship season. Serum sampling was carried out several times at baseline and after a match and/or a concussion, at set times (2, 36 h). Serum S100B concentrations were determined using chemiluminescence immunoassay on a Roche Diagnostics® instrument. The players’ basal serum S100B was stable during the season and was not correlated with anthropometric data, body composition, or creatine kinase concentration. A significant increase in S100B concentration within 2 h after a game (without concussion) was observed. This increase was correlated with the number of body collisions during a match. Seventy-seven assays were performed 36 h after a game, including the follow-up of five concussed players. Thirty-six hours after a match, an increase of a minimum of 20 % compared with individual basal concentrations identified concussion with 100 % sensitivity and 81 % specificity. S100B measured 36 h after a match is thus a discriminating test to identify concussion in a male rugby player, with a 100 % negative predictive value.

This work was supported by 2 grants attributed by the Fédération Française de Cardiologie and society ADETEC of patients with a previous cardiac surgery; If it is sustained for several days, sepsis can trigger severe abnormalities of cardiac function which leads to death in 50% of cases. This probably occurs through activation of toll‐like receptor‐9 by bacterial lipopolysaccharides and overproduction of proinflammatory cytokines such as TNF‐α and IL‐1β. In contrast, early sepsis is characterized by the development of tachycardia. This study aimed at determining the early changes in the cardiac function during sepsis and at finding the mechanism responsible for the observed changes. Sixty male Wistar rats were randomly assigned to two groups, the first one being made septic by cecal ligation and puncture (sepsis group) and the second one being subjected to the same surgery without cecal ligation and puncture (sham‐operated group). The cardiac function was assessed in vivo and ex vivo in standard conditions. Several parameters involved in the oxidative stress and inflammation were determined in the plasma and heart. As evidenced by the plasma level of TNF‐α and gene expression of IL‐1β and TNF‐α in the heart, inflammation was developed in the sepsis group. The cardiac function was also slightly stimulated by sepsis in the in vivo and ex vivo situations. This was associated with unchanged levels of oxidative stress, but several parameters indicated a lower cardiac production of reactive oxygen species in the septic group. In conclusion, despite the development of inflammation, early sepsis did not increase reactive oxygen species production and did not reduce myocardial function. The depressant effect of TNF‐α and IL‐1β on the cardiac function is known to occur at very high concentrations. The influence of low‐ to moderate‐grade inflammation on the myocardial mechanical behavior must thus be revisited.

International audience; Background:Fecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBD).Goals:We aimed to evaluate the accuracy of fecal matrix metalloprotease-9 (MMP-9) and fecal lipocalin-2 (LCN-2) compared with calprotectin in detecting endoscopic activity in IBDStudy:Overall, 86 IBD adults underwent colonoscopy consecutively and prospectively, with Crohn's disease Endoscopic Index of Severity (CDEIS) in Crohn's disease (CD) patients or Mayo endoscopic subscore calculation for ulcerative colitis (UC) patients, and stool collection. Fecal calprotectin was measured using quantitative immunochromatographic testing. Fecal MMP-9 and LCN-2 was quantified by enzyme-linked immunosorbent assay. MMP-9 and LCN-2 thresholds were determined using receiver operating curves.Results:In 54 CD patients, fecal calprotectin, MMP-9 and LCN-2 correlated with CDEIS and were significantly increased in patients with endoscopic ulcerations. MMP-9 >350 ng/g detected endoscopic ulceration in CD with a sensitivity of 90.0% and a specificity of 63.6%, compared with fecal calprotectin >250 g/g (sensitivity=90.5% and specificity=59.1%). Fecal LCN-2 demonstrated lower performances than the 2 other biomarkers (sensitivity=85.7% and specificity=45.5%).In 32 UC patients, fecal MMP-9, LCN-2, and calprotectin levels were significantly increased in patients with endoscopic activity. In UC patients, fecal MMP-9 >900 ng/g had the best efficacy to detect endoscopic activity (sensitivity=91.0% and specificity=80.0%, compared with fecal calprotectin >250 g/g (sensitivity=86.4% and specificity=80.0%) and LCN-2 >6700 ng/g (sensitivity=82.0% and specificity=80.0%).Conclusions:Fecal MMP-9 is a reliable biomarker in detecting endoscopic activity in both UC and CD patients.

Newborn screening (NBS) for inborn errors of metabolism (IEM) was introduced more than 50 years ago with the testing of phenylketonuria (PKU) using blood spots deposited on a filter paper after heel prick. NBS aims to identify early after birth inherited disorders for which clinical management and pre-symptomatic treatment will significantly decrease morbidity and mortality. While NBS for a few other disorders was implemented in some specific jurisdictions over the following decades, it is with the introduction of tandem mass spectrometry (MSMS) by the end of the 1990’s that NBS expansion really took place. MSMS has had a tremendous impact on NBS, but led to heterogeneity in NBS disorders panel between jurisdictions that have introduced new conditions at various rates using different decision-making processes. In addition to disorders tested by MSMS, many programs have included other inherited disorders using various testing methodologies, including cystic fibrosis (CF), sickle cell diseases (SCD), while some others have been recently introduced in some jurisdictions or are under considerations, such as severe combined immunodeficiency (SCID), lysosomal storage disorders and X-linked adrenoleukodystrophy (X-ALD). As the cost of DNA testing decreases, the future of NBS will inevitably include genome sequencing, which will represent an opportunity to detect, treat and prevent more serious early-onset health conditions in the best interest of newborns, provided that public health authorities rule on ethical and policy issues, such as the identification of variant of unknown significance and the disclosure of incidental findings. Finally, despite the current exciting technological advances in the field of NBS in the Northern hemisphere, we should not be blinded that despite various initiatives, about two-thirds of neonates born in low-resource areas are still waiting to have access to NBS.

International audience; Animal models of vitamin A (retinol) deficiency have highlighted its crucial role in reproduction and placentation, whereas an excess of retinoids (structurally or functionally related entities) can cause toxic and teratogenic effects in the embryo and foetus, especially in the first trimester of human pregnancy. Knock-out experimental strategies-targeting retinoid nuclear receptors RARs and RXRs have confirmed that the effects of vitamin A are mediated by retinoic acid (especially all-trans retinoic acid) and that this vitamin is essential for the developmental process. All these data show that the vitamin A pathway and metabolism are as important for the well-being of the foetus, as they are for that of the adult. Accordingly, during this last decade, extensive research on retinoid metabolism has yielded detailed knowledge on all the actors in this pathway, spurring the development of antagonists and agonists for therapeutic and research applications. Natural and synthetic retinoids are currently used in clinical practice, most often on the skin for the treatment of acne, and as anti-oncogenic agents in acute promyelocytic leukaemia. However, because of the toxicity and teratogenicity of retinoids during pregnancy, their pharmacological use needs a sound knowledge of their metabolism, molecular aspects, placental transfer, and action.

Background The acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that encompasses multiple phenotypes, e.g. with regards to lung morphology as assessed by computed tomography (CT). Focal or non-focal lung morphology may influence the response to positive end-expiratory pressure (PEEP), recruitment manoeuvres and prone position. Lung morphology has been hypothesized to be associated with alveolar fluid clearance (AFC), thus explaining various responses to such therapeutic interventions; however, this hypothesis has not been specifically studied in humans. Methods We measured net AFC rates in 30 patients with ARDS as a secondary data analysis of a prospective single-centre study. Net AFC rates were compared between patients with focal ARDS and those with non-focal ARDS, as assessed by lung CT-scans. Results Net AFC rates were significantly lower in patients with non-focal ARDS (n = 23; median [interquartile range], 1.5 [0–5.5] %/h) as compared to those with focal ARDS (n = 7; 10.3 [4.5–15] %/h) (P = 0.01). The area under the receiver-operating characteristic curve when net AFC rates were used to differentiate the presence from absence of non-focal ARDS was 0.93 (95% confidence interval, 0.81–1). Tidal volumes and PEEP levels differed between focal and non-focal ARDS patients, but there was no difference in arterial oxygenation or in alveolar-capillary permeability. Conclusions Non-focal lung morphology may be characterized by a functional endotype consistent with marked AFC impairment. Despite study limitations and the need for validating studies in larger cohorts, such novel findings may reinforce our understanding of the association between ARDS phenotypes and therapeutic responses.

International audience; Background Faecal biomarkers are emerging tools in the assessment of mucosal healing in inflammatory bowel diseases (IBDs). Aim To evaluate the accuracy of faecal chitinase 3-like 1(CHI3L1) compared to calprotectin in detecting endoscopic activity in IBD. Methods Overall, 86 IBD adults underwent colonoscopy consecutively and prospectively, with Crohn's disease Endoscopic Index of Severity (CDEIS) or Mayo endoscopic subscore calculation for ulcerative colitis, and stool collection. Faecal calprotectin was measured using quantitative immunochromatographic testing. Faecal CHI3L1 was quantified by ELISA. CHI3L1 cut-off value was determined using a receiver-operating curve. Results In 54 Crohn's disease patients, faecal CHI3L1 (rho = 0.70, P < 0.001) and calprotectin (q = 0.74, P < 0.001) levels correlated with CDEIS and were significantly increased in patients with endoscopic ulceration. In patients with ileal Crohn's disease, faecal CHI3L1 seemed to be better correlated with CDEIS than faecal calprotectin (q = 0.78 vs. rho = 0.62, P < 0.001 for both). CHI3L1 > 15 ng/g detected endoscopic ulceration in Crohn's disease with a sensitivity of 100% and a specificity of 63.6%, compared to faecal calprotectin > 250 lg/g showing a sensitivity of 90.5% and a specificity of 59.1%. In 32 ulcerative colitis patients, faecal CHI3L1 and calprotectin levels correlated with Mayo endoscopic subscore (q = 0.44 and 0.61, respectively, P < 0.001 for both) and were significantly increased in ulcerative colitis patients with endoscopic activity. In ulcerative colitis patients, faecal CHI3L1 > 15 ng/g predicted endoscopic activity with a sensitivity of 81.8% and a specificity of 80.0%, compared to faecal calprotectin> 250 lg/g showing a sensitivity of 86.4% and a specificity of 80.0%. Conclusion Faecal CHI3L1 is a reliable biomarker in detecting endoscopic activity in IBD.

Special Issue: Abstracts of the 20th Annual Meeting of French Society of Pharmacology and Therapeutics, 37th Pharmacovigilance Meeting, 17th APNET Seminar, 14th CHU CIC Meeting, 19–21 April 2016, Nancy, France; Introduction: Between September and December 2012, unusual postoperative bleedings occurred in all on-pump cardiac surgery in our heart-surgery department of Clermont- Ferrand University Hospital. This issue was concomitant to the replacement of Choay heparina by Panpharma heparin. The aim of this study isto compare the postoperative hemostasis between these two heparins.Material and methods: We retrospectively compared the operative and postoperative surgical data from patients who had undergone surgery during this 4-month period when Panpharma heparin (group P, 257 patients) was used with data from patients who had undergone surgery during the following 3 months and received Choay (group C, 194 patients).Results: There was no significant difference between the two groups in terms of preoperative characteristics, operative indications, or theoretical heparin doses.Despite group P receiving a significantly lower total dose of heparin (mean dose 21 000 IU/CEC) compared to group C (mean dose 22 000 IU/CEC) ( P = 0.05), the number of surgical re-explorations needed to perfect postoperative hemostasis was significantly higher for group P (3.5% vs. 0) (P = 0.01). Heparin anti-Xa activity after surgery had higher anticoagulant activity in group P at postoperative h1 and h12 compared to group C, which accounted for the greater postoperative surgical re-explorations in group P

Indication of cranial computed tomography (CCT) for patients with head minor injury (MHI) is difficult. Actually, 90% of patients with MHI who have CCT under the present clinical decision rules have normal scans. Serum concentrations of the protein S-100B were recently found to provide useful information. We have investigated whether S-100B concentrations in patients with MHI can provide additional information to improve indication of the need for an initial CCT scan. One hundred five patients with MHI were enrolled in this prospective study, at the French university hospital of Marseille and Clermont-Ferrand. Of the 105 patients studied, 16 exhibited trauma-relevant intracerebral lesions on the CCT scan (CCT+). With a cut-off limit of 0,10 microg/L S-100B, CCT+ patients were identified with a sensitivity level of 100% and a specificity level of 33%. Adding the measurement of S-100B serum concentration to the clinical decision rules for a CCT scan in patients with MHI could allow a 30% reduction in scans.

Background Traumatic brain injury management is a tricky issue in children and pregnant women (due to adverse effects of computer tomography). To facilitate management, we report the main analytical performances and reference ranges for blood tests for the well-established S100B biomarker in under-16 children on a DiaSorin® Liaison XL analyzer and in pregnant women on DiaSorin® Liaison XL and Roche Diagnostics® Cobas e411 analyzers. Methods Serum S100B concentrations were determined by chemiluminescent immunoassay on a DiaSorin® analyzer in a population of 409 healthy children aged 0-16 years and on DiaSorin®/Roche Diagnostics® instruments in a population of 50 pregnant women (one blood sample for each trimester). The analytical performances of both instruments and the influence of blood cells and skin pigmentation on the assay were also studied. Results For children, four age-groups emerged, i.e. 0-3 months (mean: 0.97 μg/L; standard deviation (SD): 0.36; 95th percentile: 1.55), 4-9 months (mean: 0.58 μg/L; SD: 0.30; 95th: 1.18), 10-24 months (mean: 0.31 μg/L; SD: 0.12; 95th: 0.54) and 2-16 years (mean: 0.20 μg/L; SD: 0.07; 95th: 0.32). For pregnant women, serum S100B concentrations were similar to defined ranges for adults and not significantly different between trimesters on DiaSorin® (p=0.652)/Roche Diagnostics® (p=0.877) analyzers. We also found S100B expression (protein, total mRNA) in lymphocytes, an influence of skin pigmentation, and good analytical performances for both instruments. Conclusions Data provided here is useful for interpreting serum S100B test results, in terms of preanalytical conditions, analytical performances, pediatric and pregnancy' environment.

Context: During pregnancy, aquaporins (AQPs) expressed in fetal membranes are essential for controlling the homeostasis of the amniotic volume, but their regulation by insulin was never explored in diabetic women. Objective: The aim of our study was to investigate the involvement of AQPs 1, 3, 8, and 9 expressed in fetal membranes in diabetic parturient women and the control of their expression by insulin. Design and Participants: From 129 fetal membranes in four populations (controls, type 1, type 2 [T2D], and gestational diabetes [GD]), we established an expression AQP profile. In a second step, the amnion was used to study the control of the expression and functions of AQPs 3 and 9 by insulin. Main Outcomes and Measures: The expression of transcripts and proteins of AQPs was studied by quantitative RT-PCR and ELISA. We analyzed the regulation by insulin of the expression of AQPs 3 and 9 in the amnion. A tritiated glycerol test enabled us to measure the impact of insulin on the functional characteristics. Using an inhibitor of phosphatidylinositol 3-kinase, we analyzed the insulin intracellular signaling pathway. Results: The expression of AQP3 protein was significantly weaker in groups T2D and GD. In nondiabetic fetal membranes, we showed for the amnion (but not for the chorion) a significant repression by insulin of the transcriptional expression of AQPs 3 and 9, which was blocked by a phosphatidylinositol 3-kinase inhibitor. Conclusion: In fetal membranes, the repression of AQP3 protein expression and functions observed in vivo is allowed by the hyperinsulinism described in pregnant women with T2D or GD.

Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema but is impaired in most patients with ARDS. No reliable marker of this process has been investigated to date.To verify whether sRAGE could predict AFC during ARDS.Anesthetized CD-1 mice underwent orotracheal instillation of hydrochloric acid. At specified time points, lung injury was assessed by analysis of blood gases, alveolar permeability, lung histology, AFC, and plasma/bronchoalveolar fluid measurements of proinflammatory cytokines and sRAGE. Plasma sRAGE and AFC rates were also prospectively assessed in 30 patients with ARDS.The rate of AFC was inversely correlated with sRAGE levels in the plasma and the bronchoalveolar fluid of acid-injured mice (Spearman's ρ = -0.73 and -0.69, respectively; P 10(-3)), and plasma sRAGE correlated with AFC in patients with ARDS (Spearman's ρ = -0.59; P 10(-3)). Similarly, sRAGE levels were significantly associated with lung injury severity, and decreased over time in mice, whereas AFC was restored and lung injury resolved.Our results indicate that sRAGE levels could be a reliable predictor of impaired AFC during ARDS, and should stimulate further studies on the pathophysiologic implications of RAGE axis in the mechanisms leading to edema resolution. Clinical trial registered with www.clinicaltrials.gov (NCT 00811629).

Objective Clinical and diagnostic management of traumatic brain injuries is problematic in young children. To facilitate this management, we describe blood reference ranges for the well established biomarker S100B in children younger than 3 years. Design and methods Serum S100B concentrations were determined by electro-chemiluminescence immunoassay in a population of 186 healthy children aged 0–3 years. Results Four age groups emerged, i.e. 0–3, 4–9, 10–24 and 25–36 months. We also found an interesting inverse correlation with head circumference. Conclusion This study provides useful serum S100B values from the largest cohort of healthy children aged 0–3 years old.

BACKGROUND The place of serum S100B measurement in mild traumatic brain injury (mTBI) management is still controversial. Our prospective study aimed to evaluate its utility in the largest child cohort described to date. METHODS Children younger than 16 years presenting at a pediatric emergency department within 3 h after TBI were enrolled prospectively for blood sampling to determine serum S100B concentrations. The following information was collected: TBI severity determined by using the Masters classification [1: minimal or Glasgow Coma Scale (GCS) 15, 2: mild or GCS 13–15, and 3: severe or GCS RESULTS For the 446 children enrolled, the median concentrations of S100B were 0.21, 0.31, and 0.44 μg/L in Masters groups 1, 2, and 3, respectively, with a statistically significant difference between these groups (P < 0.05). In Masters group 2, 65 CCT scans were carried out. Measurement of S100B identified patients as CCT+ with 100% (95% CI 85–100) sensitivity and 33% (95% CI 20–50) specificity. Of the 424 children scored Masters 1 or 2, 21 presented “bad CE.” S100B identified bad CE patients with 100% (95% CI 84–100) sensitivity and 36% (95% CI 31–41) specificity. Of the 242 children hospitalized, 81 presented an S100B concentration within the reference interval. CONCLUSIONS Serum S100B determination during the first 3 h of management of children with mTBI has the potential to reduce the number of CCT scans, thereby avoiding unnecessary irradiation, and to save hospitalization costs.

International audience; It has been proposed that four members of the aquaporin family (AQPs 1, 3, 8, and 9) are involved in the control of amniotic fluid (AF) homeostasis, as illustrated by their differential expression patterns in normal and pathological human term fetal membranes. However, there are no data available to date on their ontogeny throughout pregnancy. Our objective was to determine spatiotemporal expression profiles of the mRNA and proteins of all 13 members of this transmembrane channel family. For this purpose, we used healthy fetal membranes from the first, second, and third trimesters of pregnancy. Total mRNA and proteins were extracted from total membranes and from separated amnion and chorion. Quantitative PCR, Western blot, and immunohistochemistry experiments were carried out to determine the presence of AQPs and to quantify their spatiotemporal expression patterns throughout pregnancy. The WISH cell line was tested to propose a cellular model for the role of AQPs in the amnion compartment. AQP11 expression was established in amniotic membranes at term. Aquaporins 1, 3, 8, 9, and 11 mRNA and proteins were present in amnion and chorion throughout human gestation. Each AQP has a time-specific expression pattern, with AQP1 presenting the highest variation in terms of mRNA and protein levels. The WISH cell line also expressed the same five AQPs. Taken together, these results indicate that AQPs are expressed and potentially involved in the regulation of AF homeostasis throughout pregnancy. This also clearly supports the hypothesis that abnormal expression could occur at any time during pregnancy, ultimately leading to obstetrical pathologies such as polyhydramnios or oligohydramnios.

We report a case of Streptobacillus moniliformis spondylodiscitis accompanied by a psoas abscess in an 80-year-old man scratched by a rooster. S. moniliformis was identified from abscess fluid by use of 16S rRNA gene sequencing. After 18 weeks of antimicrobial therapy, the clinical condition of the patient improved.

Receptor for advanced glycation endproducts (RAGE) is a transmembrane receptor expressed in the lung and primarily located on alveolar type I cells. RAGE is implicated in acute respiratory distress syndrome to alveolar inflammation and, when its soluble form sRAGE is assayed in plasma or pulmonary edema fluid, as a marker of AT I cell injury. Functional activity of AT 1 cells can be assessed by the measurement of the alveolar fluid clearance (AFC) rate [1], but the relationship between sRAGE plasma levels of sRAGE and AFC rates has never been investigated. Our objectives were to report plasma levels of sRAGE in a mouse model of direct acid-induced epithelial injury, and to test their correlation with AFC rates.

L’evaluation du pronostic des victimes de traumatismes crâniens graves (TCG) est difficile dans la prise en charge de ces patients. Devant la faible sensibilite du score de Glasgow, la proteine S100B semble etre un bon marqueur pronostique. Cependant peu d’etudes sont basees sur des prelevements centraux en jugulaire. L’objectif de notre etude est de comparer l’interet de cinetiques arterielles et jugulaires des concentrations seriques de S100B chez le patient victime d’un TCG. Pour cela, nous avons mene une etude prospective au sein du CHU de Clermont-Ferrand, sur 17 patients orientes en service de reanimation suite a un TCG, dans le but d’evaluer l’interet d’une cinetique de dosages seriques de la proteine S100B en arteriel et en jugulaire au decours de leur prise en charge. Le dosage de la proteine S100B a demontre une concentration mediane de 0,16 μg/L en arteriel et de 0,25 μg/L en jugulaire. Pour l’ensemble des prelevements des 17 patients, la mediane de concentration arterielle en S100B est significativement differente de la mediane de concentration jugulaire. Cette difference significative arterio-jugulaire n’est pas retrouvee dans le sous-groupe des TCG de mauvaise evolution ni dans le sous-groupe des prelevements realises avant les 24 premieres heures post traumatisme. Dans le sous-groupe des TCG de mauvais pronostic, il n’existe pas, contrairement a ce que l’on observe en arteriel, de diminution significative du taux jugulaire de S100B apres les 24 premieres heures post traumatisme. En regard de ces resultats, les dosages en jugulaire semblent donc presenter un meilleur interet pronostique qu’en arteriel.